Cannabidiol improves haloperidol-induced motor dysfunction in zebrafish: a comparative study with a dopamine activating drug

BACKGROUND: Cannabidiol (CBD) extracted from the cannabis plant is believed to have a medicinal value due to its neuroprotective effect via anti-inflammatory and antioxidant action. Recent behavioral studies in rats have reported that CBD mediates serotonin (5-HT1A) receptor action to improve motor dysfunction induced by dopamine (D2) receptor blockade. In particular, its effect on D2 receptor blockade in the striatum is an important function associated with neurological disorders resulting from various extrapyramidal motor dysfunctions. Dopaminergic neurodegeneration associated with this site is known for inducing Parkinson’s disease (PD), which often affects the elderly. It is also known to cause drug-induced Parkinsonism. This study examines the ameliorating effect of CBD, which does not act directly on D2 receptors, against drug-induced motor dysfunction induced by the antipsychotic drug (haloperidol). METHODS: We created a drug-induced Parkinsonism model in zebrafish larvae using an antipsychotic drug (haloperidol). We evaluated the distance traveled and repetitive light-stimulation response. Furthermore, we examined whether administration of several concentrations of CBD ameliorates symptoms of the Parkinsonism model and compared its effects with those of antiparkinsonian drug ropinirole. RESULTS: CBD concentrations equal to half of haloperidol’s resulted in an almost complete reversal of haloperidol-induced motor dysfunction, as measured by the distance traveled by the zebrafish and their response to light-stimulus. While ropinirole also significantly reversed haloperidol’s effects at the same concentration as CBD, CBD was more effective than ropinirole. CONCLUSIONS: CBD-induced motor dysfunction improvement via D2 receptor blockade is a potential novel mechanism for the treatment of haloperidol-induced motor dysfunction.